Effect of plasmapheresis on ATG (Thymoglobulin) clearance prior to adoptive T cell transfer

Zhang, Ping; Curley, Cameron; Mudie, Kari; Nakagaki, Midori; Hill, Geoffrey R.; Roberts, Jason A.; Tey, Siok-Keen

doi:10.1038/s41409-019-0505-5

Cited by 13 publications

(8 citation statements)

References 21 publications

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“…A mainstream approach to the removal of T cells in vivo and to reducing GVHD is post-transplant cyclophosphamide (PTCy) [ 26 , 27 ]. Another effective strategy for T cell depletion in vivo is ATG [ 28 ]. ATG effectively targets alloreactive T cells from the graft, leading to T cell depletion and decreased incidence of GVHD [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Reduced Risk of Chronic Graft-Versus-Host Disease (cGVHD) by Rabbit Anti-Thymocyte Globulin (ATG) in Patients Undergoing Matched Sibling Donor Transplantation in Hematological Malignancies

Fang

Wang

et al. 2022

Ann Transplant

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Background With the addition of anti-thymocyte globulin (ATG) to GVHD prophylaxis in patients undergoing transplantation of peripheral blood stem cells (PBSCT), the incidence of cGVHD decreases. However, the optimal dose and timing of ATG remain undetermined. Material/Methods In this historical controlled trial, data from 85 patients who had hematological malignancies and underwent matched sibling donor (MSD)-PBSCT were used to analyze the effectiveness of rabbit ATG (rATG) for prophylaxis of GVHD. Forty patients received 5 mg/kg rATG used for days −5 to −2, and 45 patients did not receive ATG. Results All patients had successful engraftment except for 2 in the non-ATG group, who had platelet engraftment failure. The 2-year cumulative incidence of chronic GVHD (cGVHD) in the ATG group versus non-ATG group was 19.3% (95% CI, 8.4–33.6%) versus 61.4% (95% CI, 45.4–73.9%) ( P <0.001), and in those with moderate to severe cGVHD it was 11.0% (95% CI, 3.4–23.6%) versus 31.8% (95% CI, 18.8–45.6%) ( P =0.029), respectively. The 2-year cumulative incidence of non-relapse mortality and relapse (CIR) were 0% versus 15.5% (95% CI, 6.8–27.5%) ( P =0.018), and 53.3% (95% CI, 35.6–68.1%) versus 26.7% (95% CI, 14.9–40.0%) ( P =0.019), respectively. No differences were found in other survival outcomes. In the multivariate analysis, ATG was an independent protective factor for moderate to severe cGVHD (HR=0.314, 95% CI, 0.103–0.958, P =0.042), and was an independent poor risk factor for CIR (HR=2.337, 95% CI, 1.133–4.822, P =0.022). Conclusions ATG in our strategy was effective for prophylaxis of cGVHD, whereas the relapse rate was increased in patients with rATG.

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Section: Discussionmentioning

confidence: 99%

Reduced Risk of Chronic Graft-Versus-Host Disease (cGVHD) by Rabbit Anti-Thymocyte Globulin (ATG) in Patients Undergoing Matched Sibling Donor Transplantation in Hematological Malignancies

Fang

Wang

et al. 2022

Ann Transplant

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“…However, in this case, the presumed cause of anaphylaxis was thymoglobulin. Thymoglobulin is an antibody medication, and has been shown to be removed by plasmapheresis [14].…”

Section: Discussionmentioning

confidence: 99%

Severe Intraoperative Anaphylaxis Related to Thymoglobulin during Living Donor Kidney Transplantation

et al. 2020

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Anaphylaxis secondary to thymoglobulin (anti-thymocyte globulin) is a rare condition that can be life threatening. Thymoglobulin is a rabbit-derived T-cell depleting polyclonal immunoglobulin. It is commonly used for induction immunosuppression and/or for treatment of acute rejection in renal transplantation. We report a case of a living kidney transplant recipient who developed intraoperative anaphylactic shock secondary to thymoglobulin. The patient had a history of pet rabbit exposure. This case report highlights the importance of prompt identification and management of intraoperative anaphylaxis, which is key to a successful outcome. Induction immunosuppression selection based on patient characteristics is important. Communication between the anesthesia team and surgeons played a key role in stopping the donor surgery.

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“…For instance, suppression of pathogenic T cells in MS patients may be affected by varying rates of ATG clearance by patients ( 77 ). It may be possible to further explore the relationship between post-AHSCT clinical relapses and blood ATG clearance flow cytometrically ( 78 ), in future AHSCT MS studies.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Suppression of Circulating Proinflammatory Cytokines in Multiple Sclerosis Patients Following Autologous Haematopoietic Stem Cell Transplantation

et al. 2022

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Autologous haematopoietic stem cell transplantation (AHSCT) is a therapeutic option for haematological malignancies, such as non-Hodgkin’s lymphoma (NHL), and more recently, for autoimmune diseases, such as treatment-refractory multiple sclerosis (MS). The immunological mechanisms underlying remission in MS patients following AHSCT likely involve an anti-inflammatory shift in the milieu of circulating cytokines. We hypothesised that immunological tolerance in MS patients post-AHSCT is reflected by an increase in anti-inflammatory cytokines and a suppression of proinflammatory cytokines in the patient blood. We investigated this hypothesis using a multiplex-ELISA assay to compare the concentrations of secreted cytokine in the peripheral blood of MS patients and NHL patients undergoing AHSCT. In MS patients, we detected significant reductions in proinflammatory T helper (Th)17 cytokines interleukin (IL)-17, IL-23, IL-1β, and IL-21, and Th1 cytokines interferon (IFN)γ and IL-12p70 in MS patients from day 8 to 24 months post-AHSCT. These changes were not observed in the NHL patients despite similar pre-conditioning treatment for AHSCT. Some proinflammatory cytokines show similar trends in both cohorts, such as IL-8 and tumour necrosis factor (TNF)-α, indicating a probable treatment-related AHSCT response. Anti-inflammatory cytokines (IL-10, IL-4, and IL-2) were only transiently reduced post-AHSCT, with only IL-10 exhibiting a significant surge at day 14 post-AHSCT. MS patients that relapsed post-AHSCT exhibited significantly elevated levels of IL-17 at 12 months post-AHSCT, unlike non-relapse patients which displayed sustained suppression of Th17 cytokines at all post-AHSCT timepoints up to 24 months. These findings suggest that suppression of Th17 cytokines is essential for the induction of long-term remission in MS patients following AHSCT.

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Effect of plasmapheresis on ATG (Thymoglobulin) clearance prior to adoptive T cell transfer

Cited by 13 publications

References 21 publications

Reduced Risk of Chronic Graft-Versus-Host Disease (cGVHD) by Rabbit Anti-Thymocyte Globulin (ATG) in Patients Undergoing Matched Sibling Donor Transplantation in Hematological Malignancies

Reduced Risk of Chronic Graft-Versus-Host Disease (cGVHD) by Rabbit Anti-Thymocyte Globulin (ATG) in Patients Undergoing Matched Sibling Donor Transplantation in Hematological Malignancies

Severe Intraoperative Anaphylaxis Related to Thymoglobulin during Living Donor Kidney Transplantation

Long-Term Suppression of Circulating Proinflammatory Cytokines in Multiple Sclerosis Patients Following Autologous Haematopoietic Stem Cell Transplantation

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